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Pnas11138correction 14002..14003 Corrections MEDICAL SCIENCES Correction for “Regulation of bone remodeling by vasopressin New, Alberta Zallone, and Mone Zaidi, which appeared in issue 46, explains the bone loss in hyponatremia,” by Roberto Tamma, November 12, 2013, of Proc Natl Acad Sci USA (110:18644–18649; Li Sun, Concetta Cuscito, Ping Lu, Michelangelo Corcelli, first published October 28, 2013; 10.1073/pnas.1318257110). Jianhua Li, Graziana Colaianni, Surinder S. Moonga, Adriana The authors note that Fig. 1 appeared incorrectly. The cor- Di Benedetto, Maria Grano, Silvia Colucci, Tony Yuen, Maria I. rected figure and its legend appear below. Fig. 1. Bone cells express Avprs. Immunofluorescence micrographs (A) and Western immunoblotting (B) show the expression of Avpr1α in osteoblasts and osteoclasts, and as a function of osteoblast (mineralization) and osteoclast (with Rankl) differentiation. The expression of Avp (ligand) and Avpr1α (receptor) in osteoblasts is regulated by 17β-estradiol, as determined by quantitative PCR (C) and Western immunoblotting (D). (Magnification: A,63×.) Because Avp is a small peptide, its precursor neurophysin II is measured. Statistics: Student t test, P values shown compared with 0 h. Stimulation of Erk phosphorylation − (p-Erk) as a function of total Erk (t-Erk) by Avp (10 8 M) in osteoclast precursors (preosteoclasts), osteoclasts (OC), and osteoblasts establishes functionality of − the Avpr1α in the presence or absence of the receptor inhibitor SR49059 (10 8 M) (E). Western immunoblotting showing the expression of Avpr2 in pre- −/− osteoclasts, OCs (F), and osteoblasts (G) isolated from Avpr1α mice, as well as in MC3T3.E1 osteoblast precursors (G). Functionality of Avpr2 was confirmed −/− by the demonstration that cells from Avpr1α mice remained responsive to AVP in reducing the expression of osteoblast differentiation genes, namely Runx2, Osx, Bsp, Atf4, Opn, and Osteocalcin (quantitative PCR, P values shown) (H). Only relevant bands from Western blots are shown, with gaps introduced where empty lanes are excised to conserve space. www.pnas.org/cgi/doi/10.1073/pnas.1415306111 14002–14003 | PNAS | September 23, 2014 | vol. 111 | no. 38 www.pnas.org Downloaded by guest on September 27, 2021 PHARMACOLOGY PHYSIOLOGY Correction for “Arrhythmias, elicited by catecholamines and Correction for “Hypothalamic prolyl endopeptidase (PREP) serotonin, vanish in human chronic atrial fibrillation,” by Torsten regulates pancreatic insulin and glucagon secretion in mice,” by Christ, Nadiia Rozmaritsa, Andreas Engel, Emanuel Berk, Michael Jung Dae Kim, Chitoku Toda, Giuseppe D’Agostino, Caroline J. Knaut, Katharina Metzner, Manuel Canteras, Ursula Ravens, Zeiss, Ralph J. DiLeone, John D. Elsworth, Richard G. Kibbey, and Alberto Kaumann, which appeared in issue 30, July 29, 2014, Owen Chan, Brandon K. Harvey, Christopher T. Richie, Mari of Proc Natl Acad Sci USA (111:11193–11198; first published Savolainen, Timo Myöhännen, Jin Kwon Jeong, and Sabrina Diano, July 14, 2014; 10.1073/pnas.1324132111). which appeared in issue 32, August 12, 2014, of Proc Natl Acad The authors note that an additional affiliation should be listed Sci USA (111:11876–11881; first published July 28, 2014; 10.1073/ for Torsten Christ and Alberto Kaumann. The new affiliation pnas.1406000111). should appear as Department of Experimental Pharmacology and The authors note that the author name Timo Myöhännen Toxicology, University Medical Center Hamburg-Eppendorf. The should instead appear as Timo Myöhänen. The corrected author corrected author and affiliation lines appear below. The online line appears below. The online version has been corrected. version has been corrected. Jung Dae Kim, Chitoku Toda, Giuseppe D’Agostino, Torsten Christa,b, Nadiia Rozmaritsaa, Andreas Engela, Caroline J. Zeiss, Ralph J. DiLeone, John D. Elsworth, Emanuel Berka, Michael Knautc, Katharina Metznera, Richard G. Kibbey, Owen Chan, Brandon K. Harvey, Manuel Canterasd, Ursula Ravensa, and Christopher T. Richie, Mari Savolainen, Timo Myöhänen, Alberto Kaumannb,e Jin Kwon Jeong, and Sabrina Diano Departments of aPharmacology and Toxicology and cHeart Surgery, www.pnas.org/cgi/doi/10.1073/pnas.1416210111 Dresden University of Technology, 01307 Dresden, Germany; bDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany; and Departments of dBiostatistics and ePharmacology, University of Murcia, 30100 Murcia, Spain www.pnas.org/cgi/doi/10.1073/pnas.1416216111 CORRECTIONS PNAS | September 23, 2014 | vol. 111 | no. 38 | 14003 Downloaded by guest on September 27, 2021 Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation Torsten Christa,b,1,2,3, Nadiia Rozmaritsaa,1,4, Andreas Engela,5, Emanuel Berka,6, Michael Knautc, Katharina Metznera,7, Manuel Canterasd, Ursula Ravensa, and Alberto Kaumannb,e,2 Departments of aPharmacology and Toxicology and cHeart Surgery, Dresden University of Technology, 01307 Dresden, Germany; bDepartment of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany; and Departments of dBiostatistics and ePharmacology, University of Murcia, 30100 Murcia, Spain Edited* by Lutz Birnbaumer, National Institute of Environmental Health Sciences, Research Triangle Park, NC, and approved June 23, 2014 (received for review December 30, 2013) Atrial fibrillation (AF) is the most common heart rhythm disorder. Increased propensity to generate spontaneous impulses is as- Transient postoperative AF can be elicited by high sympathetic sumed to initiate and/or maintainAFinhumans.Arrhythmiasmay nervous system activity. Catecholamines and serotonin cause ar- develop through spontaneous impulse generation within individual rhythmias in atrial trabeculae from patients with sinus rhythm (SR), myocytes and/or reentry around nonexcitable tissue. The traveling but whether these arrhythmias occur in patients with chronic AF is electrical impulse of a premature atrial beat can encounter areas of unknown. We compared the incidence of arrhythmic contractions refractoriness, return to its origin in a retrograde way, and through caused by norepinephrine, epinephrine, serotonin, and forskolin in reentry initiate and maintain AF. Spontaneous impulse generation atrial trabeculae from patients with SR and patients with AF. In the could be related to increased activity of PKA and/or CaMKII, with + patients with AF, arrhythmias were markedly reduced for the subsequent uncoordinated release of Ca2 from the sarcoplasmic + agonists and abolished for forskolin, whereas maximum inotropic reticulum. Such a concept is attractive, because Ca2 released from + + responses were markedly blunted only for serotonin. Serotonin and the “leaky” sarcoplasmic reticulum would activate the Na -Ca2 2+ + forskolin produced spontaneous diastolic Ca releases in atrial myo- exchanger to extrude Ca2 and to produce a arrhythmogenic cytes from the patients with SR that were abolished or reduced 2+ depolarizing current, thereby explaining both the contractile in myocytes from the patients with AF. For matching L-type Ca - dysfunction and the high recurrence rate (11–13). current (ICa,L) responses, serotonin required and produced ∼100-fold 2+ If arrhythmias were initiated and maintained by increased less cAMP/PKA at the Ca channel domain compared with the cat- activity of PKA and/or CaMKII, then interventions known to echolamines and forskolin. Norepinephrine-evoked ICa,L responses + were decreased by inhibition of Ca2 /calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from Significance patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was re- Catecholamines and serotonin elicit arrhythmias in atrial tra- 2+ duced in trabeculae from patients with AF. The decreased CaMKII beculae and arrhythmogenic diastolic Ca releases in myocytes activity may contribute to the blunting of agonist-evoked arrhyth- from patients with normal sinoatrial rhythm (SR). Arrhythmic mias in the atrial myocardium of patients with AF. events are greatly blunted in the myocardium of patients with chronic atrial fibrillation (AF). The mediation by cyclic AMP- + dependent protein kinase of L-type Ca2 -current (I ) responses trial fibrillation (AF) is the most common cardiac arrhythmia, Ca,L to agonists, lusitropy, and protein phosphorylation are preserved associated with increased risk of death, congestive heart fail- A in AF. The vanishing of agonist-evoked arrhythmias in AF is as- ure, and stroke (1). AF is characterized by an irregular, often rapid sociated with the disappearance of an ICa,L response, facilitated by heart rate. Atria contract with reduced force, thereby favoring 2+ Ca /calmodulin-dependent kinase II (CaMKII), in myocytes from PHARMACOLOGY thrombus formation (2). AF occurs in several cardiac diseases, and patients with SR, and decreased phosphorylation of phospho- its incidence is higher in woman than in men, particularly in those SI Appendix lamban, but not ryanodine, by this enzyme. The disappearance of with valvular heart disease ( , Table S1). Chronic AF arrhythmias and associated reduction of CaMKII functions causes structural and electrical remodeling, as well as enlarged atria questions the use of CaMKII inhibitors in AF, as has been pro- SI Appendix ( ,TableS1),whichinturncontributestomaintainAF. posed by other groups. Atrial contractility is reduced in isolated atrial
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